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Defects in cervical vertebrae in boric acid-exposed rat embryos are associated with anterior shifts of hox gene expression domains.

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Wéry, Nathalie Narotsky, Michael G Pacico, Nathalie Kavlock, Robert J Picard, Jacques [UCL] Gofflot, Françoise [UCL]

BACKGROUND: Previously, we showed that prenatal exposure to boric acid (BA), an industrial agent with large production, causes alterations of the axial skeleton in rat embryos, reminiscent of homeotic transformations. Indeed, Sprague-Dawley rats exposed in utero to BA on gestation day 9 (GD 9) had only six, rather than the normal seven, cervical vertebrae. This finding, observed in 91% of GD 21 fetuses, suggests posterior transformations of vertebrae. The present study attempts to determine if these skeletal alterations could be explained by modifications of the hox code, involved in the establishment of positional information along the craniocaudal axis of the embryo. METHODS: Pregnant rats were treated by gavage with BA (500 mg/kg, twice) on GD 9. Embryos were collected on GD 11 or GD 13.5 and processed for in situ hybridization. Several hox genes were selected according to the position of their cranial limit of expression in the cervical and thoracic region. RESULTS: At GD 13.5, we detected a cranial shift of the anterior limit of expression of hoxc6 and hoxa6. We observed no difference between control and treated embryos in the location of the cranial limit of expression of the other genes: hoxd4, hoxa4, hoxc5, and hoxa5. CONCLUSIONS: Our results demonstrate that following in utero exposure to BA on GD 9, a disturbance of the expression of hox genes involved inthe specification of most anterior vertebrae is observed at GD 13.5. Based on their expression domain and on their implication in the definition of the cervicothoracic vertebral boundary, it is likely that the anteriorization of hoxc6 and hoxa6 reported here is correlated to the morphological phenotype observed in BA-exposed fetuses at GD 21.

Document type Article de périodique (Journal article) – Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.
Access type Accès restreint
Publication date 2003
Journal information "Birth defects research. Part A, Clinical and molecular teratology" - Vol. 67, no. 1, p. 59-67 (2003)
Peer reviewed yes
issn 1542-0752
Publication status Publié
Affiliation UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique
MESH Subject Animals ; Boric Acids - toxicity ; Cervical Vertebrae - abnormalities - drug effects - embryology ; Female ; Gene Expression Regulation, Developmental ; Genes, Homeobox ; In Situ Hybridization ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Teratogens - toxicity
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Bibliographic reference Wéry, Nathalie ; Narotsky, Michael G ; Pacico, Nathalie ; Kavlock, Robert J ; Picard, Jacques ; et. al. Defects in cervical vertebrae in boric acid-exposed rat embryos are associated with anterior shifts of hox gene expression domains.. In: Birth defects research. Part A, Clinical and molecular teratology, Vol. 67, no. 1, p. 59-67 (2003)
Permanent URL http://hdl.handle.net/2078.1/9457